tbuckley/cabot-search huggingface dataset:
Abstract 286: Patient derived explant culture (PDEC) as a model for treatment resistant ERα positive breast cancers
Authors: Pauliina Munne, Iiris Räty, Aino Peura, Linda Patrikainen, Denis Belitskin, Juha Klefstrom
Journal: Cancer Research (2022)

Abstract Breast cancer is the most frequent cancer and leading causes of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα+) phenotype that is initially responsive to antihormonal therapies, but often drug resistance emerges. Three-dimensional ex vivo cultures from patient-derived tumor tissue offer new opportunities for drug development and personalized treatment of cancer. However, one of the main challenges in establishing a tumor type faithful ex vivo tissue culture system is in optimization of biochemical and physical microenvironment to preserve desired phenotypic features. The ERα+ phenotype is not stable in cultured cells for reasons not fully understood. Together with Helsinki University Hospital we examined 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. In our current study we have utilized the PDEC model to identify novel biomarkers that could predict the emergence of tamoxifen resistance in primary breast tumors. Citation Format: Pauliina Munne, Iiris Räty, Aino Peura, Linda Patrikainen, Denis Belitskin, Juha Klefstrom. Patient derived explant culture (PDEC) as a model for treatment resistant ERα positive breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 286.
Abstract 2446: Low dose dimethyl sulfoxide (DMSO) downregulates the expression of androgen receptor (AR) and AR-variant 7 (AR-v7) in castration resistant prostate cancer (CRPC) cells
Authors: Namrata Khurana, Hogyoung Kim, Talal Khan, Shohreh Kahhal, Amar Bukvic, Asim B. Abdel-Mageed, Suresh C. Sikka, Debasis Mondal
Journal: Cancer Research (2022)

Abstract The highly aggressive prostate cancer (PC) cells utilize androgen receptor (AR) signaling to facilitate their growth and metastasis. Despite androgen deprivation therapy (ADT), recurrence of castration-resistant prostate cancer (CRPC) often occur due to constitutive AR signaling via both full-length AR (AR-FL) and AR splice variants, primarily AR-V7. Therefore, safe strategies to suppress both AR-FL &amp; AR-V7 expression in CRPC cells will be of significant benefit. Several plant-derived organosulfur compounds, e.g. sulforaphane and diallyl-trisulfide, can potently suppress AR expression in CRPC cells, but are yet to be clinically approved. We investigated whether dimethyl sulfoxide (DMSO) an approved organosulfur compound often used as a solvent for pharmaceutical agents, can similarly suppress AR levels in the CRPC cell lines, C4-2B and 22Rv1. Exposure to low dose DMSO (0.1-1%) was not cytotoxic to these CRPC cells, and less than 20% cytotoxicity was seen with 2.5% DMSO even at 96 h post-exposure. Interestingly however, DMSO dose-dependently suppressed AR-FL in C4-2B cells and both AR-FL and AR-V7 in 22Rv1 cells within 24 h post-exposure. Exposure to DMSO also downregulated the expression of hetero-nuclear ribonucleoprotein H1 (hnRNPH1), which is known to regulate AR expression and splicing. Although DMSO exposure showed a dose- and time-dependent effect on reactive oxygen species (ROS) production by PC cells, the AR-suppressive effect of DMSO was not altered by the antioxidant n-acetyl cysteine (NAC). Furthermore, although DMSO did not affect cell viability at these clinically-achievable concentrations, a significant (p&amp;lt;0.01) decrease in the migratory ability of both CRPC cell lines was clearly evident. Our novel findings indicate that safe doses of DMSO may be used to decrease AR expression and metastatic ability in CRPC cells. Citation Format: Namrata Khurana, Hogyoung Kim, Talal Khan, Shohreh Kahhal, Amar Bukvic, Asim B. Abdel-Mageed, Suresh C. Sikka, Debasis Mondal. Low dose dimethyl sulfoxide (DMSO) downregulates the expression of androgen receptor (AR) and AR-variant 7 (AR-v7) in castration resistant prostate cancer (CRPC) cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2446.
Abstract 301: Repurposing engineered thymoquinone nanoparticles to inhibit drug-resistant prostate cancer
Authors: Santosh Kumar Singh, Manoj Kumar Mishra, Rajesh Singh
Journal: Cancer Research (2022)

Abstract Despite advanced treatment strategies and therapeutics for prostate cancer (PCa), the metastatic castration-resistant prostate cancer (mCRPC) mechanism remains obscure. Although docetaxel (DTX) and other anti-mitotic chemotherapeutic drug are considered the first line drugs for PCa patients; the resulting side effects and drug resistance increase the demand for an alternative such as natural compounds for effective treatment. However, the natural compounds that achieved remarkable height to overcome drug resistance, their bioavailability and targeted delivery during treatment has become a new challenge. As prostate-specific membrane antigen (PSMA) receptors are expressed on the surface of most PCa cells, we anticipated that these receptors may provide the potential target for effective therapy. Considering these, we employed the natural compound, thymoquinone (TQ)-encapsulated planetary ball-milled nanoparticles (PBM-NPs) formulated with starch (FDA approved, natural polysaccharides) inner core and biocompatible and biodegradable co-polymers poly (ε-caprolactone)/poly (ethylene glycol), functionalized with a PSMA aptamer (A10), which can selectively recognize and bind to PSMA membrane. The functionalities of this strategy were analyzed by targeting A10-TQ-PBM-NP in DTX-resistant cells (C4-2B-R and LNCaP-R), which overexpresses PSMA protein and multidrug resistance (MDR) gene ABCB1, and validated through flow cytometry, immunofluorescence, qRT-PCR, and western blot techniques. The results showed that the aptamer-based nano delivery of a TQ can modulate the cellular and molecular pathways responsible for DTX resistance in PCa cells through the EGFR and ZEB1 dependent mechanism. The A10-TQ-PBM-NPs counteract ATP-binding cassette (ABC)-transporter-mediated chemoresistance in PCa cells. In both cell lines, these NPs rapidly internalized and induced significant cell death at five times lower concentrations than non-conjugated PBM-TQ-NP. Further, A10-TQ-PBM-NPs have high selectivity to the PSMA receptor and downregulated the EGFR dependent pathway, Akt-1, ERK1/2, NF-kB, STAT3, and epithelial-mesenchymal transition (EMT) markers in both C4-2B-R and LNCaP-R cells, thus constraining cell survival, proliferation, and migration. The A10-TQ-PBM-NP bioconjugates also reveal remarkable efficacy and reduced toxicity as measured by body weight loss in the LNCaP-R cells xenograft mice. Altogether, our findings demonstrate that targeting PCa cells with PBM-NPs may reverse the MDR and could be used as potential therapeutic options for patients. Citation Format: Santosh Kumar Singh, Manoj Kumar Mishra, Rajesh Singh. Repurposing engineered thymoquinone nanoparticles to inhibit drug-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 301.
Abstract 1927: Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning
Authors: Shan-Ju Yeh, Ruoqiao Chen, Jing Xing, Mengying Sun, Ke Liu, Shreya Paithankar, Jiayu Zhou, Bin Chen
Journal: Cancer Research (2022)

Abstract Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. We present TransCell, a two-step deep transfer learning framework that utilizes the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Compared to the five state-of-art methods, TransCell has the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and has comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, TransCell demonstrates its remarkable predictive power that enables in silico molecular characterization of understudied cell lines. Citation Format: Shan-Ju Yeh, Ruoqiao Chen, Jing Xing, Mengying Sun, Ke Liu, Shreya Paithankar, Jiayu Zhou, Bin Chen. Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1927.
Abstract 3712: The C-terminal HSP90 inhibitor, a novel deguelin derivative, exerts anti-metastatic effects in triple-negative breast cancer by targeting cancer stem-like properties
Authors: Minsu Park, Tae-Min Cho, Soeun Park, Jung Min Park, Juyeon Seo, Dongmi Ko, Seongjae Kim, So Ra Seuk, Yong Gu Kang, Kee Dal Nam, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo
Journal: Cancer Research (2022)

Abstract Purpose: Triple-negative breast cancer (TNBC) still relies on non-selective cytotoxic anticancer agents due to the absence of established molecular targets for the phenotype. The heat shock protein 90 (HSP90) is a promising therapeutic target because it affects the overall progression of cancer, including cell proliferation, angiogenesis and metastasis. A variety of N-terminal HSP90 inhibitors have been tried several times in clinical trials, but none have been approved for clinical use to date due to issues including heat shock response (HSR) induction, undesirable effects, and clinical toxicity. In this study, we sought to investigate whether a novel C-terminal HSP90 inhibitor SL-145 could resolve metastasis in TNBC through inhibition of cancer stem-like properties. Experimental Design: The effects of SL-145 on TNBC cell lines in vitro were evaluated in terms of cell proliferation, apoptosis, caspase-3 activity, breast cancer stem cell (BCSC)-like properties and heat shock response. An orthotopic allograft model with 4T1 mammospheres was used to examine the effect of SL-145 on tumor growth and metastasis in vivo. Results: SL-145 induces apoptosis without triggering the HSR and simultaneously inhibits several oncogenic signaling pathways including AKT, MEK/ERK and JAK2/STAT3. SL-145 effectively targets BCSC-like properties with significant reductions in CD44, CD49f and ALDH1 expression as well as impairment of mammosphere-forming ability. To confirm the physiological relevance of our in vitro observations, we investigated the effects of SL-145 on tumor growth, angiogenesis and metastasis in mammosphere-derived allograft tumors with self-renewal capacity. SL-145 administration reduced tumor burden and angiogenesis, which were enriched in BCSCs, and it resulted in significant reductions in lung and liver metastases. In addition, no toxic effects of inhibitors on markers of liver or renal function were observed. Conclusion: Our findings suggest that SL-145 may represent an effective therapeutic approach for targeting cancer stem cells and simultaneous inhibition of the HSP90 client oncoprotein to treat TNBC with a heterogeneous and aggressive nature. Citation Format: Minsu Park, Tae-Min Cho, Soeun Park, Jung Min Park, Juyeon Seo, Dongmi Ko, Seongjae Kim, So Ra Seuk, Yong Gu Kang, Kee Dal Nam, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo. The C-terminal HSP90 inhibitor, a novel deguelin derivative, exerts anti-metastatic effects in triple-negative breast cancer by targeting cancer stem-like properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3712.
Abstract 3843: TIMP1 and TIMP2 re-educate TGFβ induced pro-inflammatory/pro angiogenic decidual-like NK cells phenotype
Authors: Adriana Albini, Matteo Gallazzi, Maria Teresa Palano, Valentina Carlini, Luana Calabrone, Riccardo Ricotta, William G. Stetler-Stevenson, Douglas M. Noonan
Journal: Cancer Research (2022)

Abstract Background: Tissue inhibitors of metalloproteases (TIMPs) have been reported to exert dual roles in cancer, based on the different cancer type and interactions with the tumor microenvironments. As inhibitors of Matrix metalloproteases (MMP) they downregulate invasion, metastasis and angiogenesis. However, TIMP1 levels have been found increased in patients with different types of cancer. Natural Killer cells have been found to be phenotypically and functionally compromised in several solid and hematological cancers. We were the first in characterizing NK pro-angiogenic phenotype in the peripheral blood and tumor tissues of patients with Non-small Cell Lung cancer, colorectal cancers, prostate of patients. Also, we found that pro-angiogenic NK cells in the peripheral blood of colorectal cancer patients release of TIMP-1 and TIMP-2, in a STAT3/STAT5-independent manner. Here, we investigated the effects of TIMP-1 and TIMP-2 recombinant proteins, using a TGFβ-mediated NK cell polarization model, in vitro. Methods: We investigated the effects of TIMP1 and TIMP2 recombinant proteins in hindering decidual-like markers in NK cells, generated by polarizing cytolytic NK cells with TGFβ. The effects of TIMP1 or TIMP2 on NK cell surface antigens were determined by multicolor flow cytometry. Results: We found that TIMP1 and TIMP2 were effective in interfering with TGFβ induced NK cell polarization towards a decidual-like-phenotype. TIMP1 and TIMP2 counteracted the effect of TGFβ in increasing the percentage of CD56bright, CD16-, CD9+ and CD49a+, and restoring normal levels for TIMP 1 and 2 also inhibited decrease levels of the activation marker NKG2D induced by TGFβ and decreased the TGFβ upregulated exhaustion marker TIM-3. NK cell degranulation capabilities against K562 cells were also decreased by TGFβ and not by TIMP1 or TIMP2. TIMP1 treatment could partially restore degranulation marker CD107a expression. Conclusions: Our results suggest a potential role of TIMPs in controlling the tumor-associated cytokine TGFβ-induced NK cell polarization. TGFβ stimulation represents a model to prove TIMP's new properties, further studies will help defining TIMPs immunomodulatory activities of NK cells in cancer, and their possible future diagnostic-therapeutic roles. Citation Format: Adriana Albini, Matteo Gallazzi, Maria Teresa Palano, Valentina Carlini, Luana Calabrone, Riccardo Ricotta, William G. Stetler-Stevenson, Douglas M. Noonan. TIMP1 and TIMP2 re-educate TGFβ induced pro-inflammatory/pro angiogenic decidual-like NK cells phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3843.
Abstract 3606: Lenalidomide switch control of CAR T-cell phenotype and function via degradable membrane-bound IL-7
Authors: Michael C. Kann, Alexander Tepper, Harrison J. Silva, Isabel C. Lane, Amanda A. Bouffard, Rebecca C. Larson, Benjamin L. Ebert, Marcela V. Maus, Max Jan
Journal: Cancer Research (2022)

Abstract CAR T cells have had marked success in the treatment of hematologic malignancies such as B-cell acute lymphoblastic leukemia and multiple myeloma. However, some patients fail to have sustained responses, in large part to due limited persistence of their CAR T cells. Previous attempts to prolong CAR T cell survival have attempted to combine CAR T cell therapy and cytokine therapy (IL-2, IL-15) to increase persistence, but this combination of T cell activation and high levels of systemic cytokines can lead to toxicities. To enhance CAR T cell persistence and while mitigating potential cytokine toxicities, we present a bicistronic CAR T engineered to express a membrane-bound drug-degradable IL-7 (mbdIL7) on its surface in addition to a 2nd generation anti-CD19 CAR. The mbdIL7 is composed of an IL-7 molecule anchored to the cell by a CD80 hinge/transmembrane domain and followed by a cytoplasmic super-degron tag and drives JAK/STAT5 signal transduction. Both mbdIL7 abundance and STAT5 phosphorylation can be efficiently suppressed with lenalidomide, an FDA approved drug, at sub-therapeutic doses. The mbdIL7 can supplant the requirement of exogenous cytokines during manufacturing and leads to a more central memory-biased T cell phenotype. mbdIL7 CAR T cell proliferation remains antigen-dependent. These novel mbdIL7 CAR T cells have similar in vitro effects to traditional CAR T against models of leukemia and lymphoma, but have distinct transcriptional profiles associated with lower levels of exhaustion. In an orthotopic xenograft lymphoma model, mbdIL7 CAR T cells demonstrate markedly enhanced anti-tumor activity compared to traditional anti-CD19 CAR T cells. In addition, mbdIL7 CAR T cells have increased expansion/persistence in the blood, bone marrow, and spleen. The inclusion of a membrane-bound degradable IL-7 into the backbone of a traditional anti-CD19 CAR allows for spatial and temporal control of a pro-persistence cytokine leading to a more effective CAR T treatment. This presents a potential controllable CAR T for patients that are currently not responding conventional FDA-approved products. Citation Format: Michael C. Kann, Alexander Tepper, Harrison J. Silva, Isabel C. Lane, Amanda A. Bouffard, Rebecca C. Larson, Benjamin L. Ebert, Marcela V. Maus, Max Jan. Lenalidomide switch control of CAR T-cell phenotype and function via degradable membrane-bound IL-7 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3606.
High-Intensity Interval Training vs Moderate-Intensity Continuous Training for Women Receiving Cardiovascular Rehabilitation—Reply
Authors: Sherrie Khadanga, Patrick D. Savage, Philip A. Ades
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Aiming for the Cure in <i>ERBB2</i>-Positive Metastatic Breast Cancer—Should We Go “All In”?
Authors: Bruno Henrique Rala de Paula, Susanne Crocamo
Journal: JAMA Oncology (2022)

To the Editor After reading the Review by Tarantino et al1 recently published in JAMA Oncology, we became very excited to hopefully see a change in the paradigms for ERBB2-positive metastatic breast cancer (MBC) but also intrigued by some provocative suggestions.
Abstract 5091: The early change of serum interleukin 14α levels predicts the response to anti-PD-1 therapy in cancer
Authors: Bu Hai Wang, Cai Yue Chen, Xian Zhang, Yu Xiang Huang, Yi Chun Zeng, Lei Li, Mao Qi Wang, Jing Liang Guo, Qiu Xian Li, Long Shen, Juan J. Gu, Yi Chen Liang
Journal: Cancer Research (2022)

Abstract Background: Targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) has been shown improved clinical efficacy in a wide range of tumor types. We evaluated serum interleukin 14α (IL14α) as a biomarker to predict the response of anti- PD-1 therapy. Patients and methods: Thirty advanced cancer patients treated with PD-1 inhibitor were enrolled in this study. Serum levels of IL-14α were tested at baseline and after 2 cycles of treatment. Result: Among these 30 patients, the mean expression level of IL14α before treatment was 2.1±1.21, whereas the mean level of IL14α after 2 cycles was 1.99±0.82. There were no association between the expression levels of IL14α and clinical outcome. Early change of IL14α after 2-cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles - IL14α level before treatment)/IL14α level before treatment*100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (Sensitivity 85.71%, Specificity 62.5%; AUC=0.7277, P=0.034). Using this cutoff to subgroup the patients, we found higher delta IL14α % change was significantly associated with superior overall response to anit-PD-1 therapy (p=0.0072) and had a better progression free survival (p=0.0039). Conclusion: Early changes of serum IL14α level may be a useful predicting factor in advanced cancer patients with anti-PD-1 therapy. Keywords: IL14α, serum biomarker, anti-PD-1 therapy response, cancer Citation Format: Bu Hai Wang, Cai Yue Chen, Xian Zhang, Yu Xiang Huang, Yi Chun Zeng, Lei Li, Mao Qi Wang, Jing Liang Guo, Qiu Xian Li, Long Shen, Juan J. Gu, Yi Chen Liang. The early change of serum interleukin 14α levels predicts the response to anti-PD-1 therapy in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5091.